CIDRAP-Trial data explains failure of invasive E coli vaccine

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Trial data explains failure of invasive E coli vaccine

www.cidrap.umn.edu

Trial data explains failure of invasive E coli vaccine​

Chris Dall, MA

Today at 11:54 a.m.
Adult (non-flu) Vaccines

E coli

Antimicrobial Stewardship


New data published this week in The Lancet Infectious Diseases reveals why a phase 3 trial for a vaccine targeting extraintestinal pathogenic Escherichia coli (ExPEC) was discontinued early last year.

The data are from the E.mbrace study, a randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy, safety, and immunogenicity of ExPEC9V, a vaccine developed jointly by Janssen Pharmaceuticals and Sanofi for the prevention of invasive E coli disease (IED) in older adults. ExPEC9V targets the nine E coli strains that cause most cases of IED—which occurs when the bacterium enters the bloodstream, urinary tract, or other sterile sites—in older adults.

ExPEC strains cause an estimated 10 million cases of IED annually and are a leading cause of sepsis, particularly in older adults with chronic illnesses. In addition, treatment has become complicated by antibiotic resistance, with one multi-country study estimating that at least 10% of E coli bloodstream isolates are multidrug-resistant. Vaccines that prevent IED are considered a key unmet medical need.

Immune response didn’t translate into efficacy​

The trial began in 2021 and enrolled more than 17,000 adults aged 60 and older in 20 countries. Participants had a history of urinary tract infections and were randomly assigned 1:1 to receive ExPEC9V or placebo. The primary end point was the incidence of IED in blood or other sterile sites caused by ExPEC9V strains.

A single dose of ExPEC9V elicited a robust and sustained antibody response, with no safety concerns. At one year after vaccination, binding antibodies in the ExPEC9V recipients remained higher than those in the placebo group.

With no established correlates of protection, vaccine-induced immunity might have been of insufficient magnitude or quality to provide clinical protection against IED and related events.

But a prespecified analysis of the primary end point by an independent data monitoring committee found 11 cases of IED in the ExPEC9V group and 13 in the placebo group, yielding a vaccine efficacy of 14.6%, indicating no protective effect. A similar lack of efficacy was found in subgroup analyses.

“Despite durability through at least the first year, the immune response did not translate into vaccine efficacy, with most IED cases occurring within year 1,” the investigators wrote. “With no established correlates of protection, vaccine-induced immunity might have been of insufficient magnitude or quality to provide clinical protection against IED and related events.”

They add that further analysis of the data, including the E coli isolated from IED cases in the trial, is needed to fully understand why the vaccine failed to offer protection against IED.

Johnson & Johnson, which owns Janssen Pharmaceuticals, announced on February 13, 2025, that the vaccine was not likely to meet its primary end point and that the trial was being discontinued.